A dysregulated immune system is a major driver of the mortality and long-term morbidity from sepsis. With respect to macrophages, it has been shown that phenotypic changes are critical to effector ...function in response to acute infections, including intra-abdominal sepsis. Invariant natural killer T cells (iNKT cells) have emerged as potential central regulators of the immune response to a variety of infectious insults. Specifically, various iNKT cell:macrophage interactions have been noted across a spectrum of diseases, including acute events such as sepsis. However, the potential for iNKT cells to affect peritoneal macrophages during an abdominal septic event is as yet unknown.
Cecal ligation and puncture (CLP) was performed in both wild type (WT) and invariant natural killer T cell knockout (iNKT−/−) mice. 24 h following CLP or sham operation, peritoneal macrophages were collected for analysis. Analysis of macrophage phenotype and function was undertaken to include analysis of bactericidal activity and cytokine or superoxide production.
Within iNKT−/− mice, a greater degree of intraperitoneal macrophages in response to the sepsis was noted. Compared to WT mice, within iNKT−/− mice, CLP did induce an increase in CD86+ and CD206+, but no difference in CD11b+. Unlike WT mice, intra-abdominal sepsis within iNKT−/− mice induced an increase in Ly6C-int (5.2% versus 14.9%; P < 0.05) and a decrease in Ly6C-high on peritoneal macrophages. Unlike phagocytosis, iNKT cells did not affect macrophage bactericidal activity. Although iNKT cells did not affect interleukin-6 production, iNKT cells did affect IL-10 production and both nitrite and superoxide production from peritoneal macrophages.
The observations indicate that iNKT cells affect specific phenotypic and functional aspects of peritoneal macrophages during polymicrobial sepsis. Given that pharmacologic agents that affect iNKT cell functioning are currently in clinical trial, these findings may have the potential for translation to critically ill surgical patients with abdominal sepsis.
Most patients with acute Paget-Schroetter syndrome (PSS) present in one of two manners: (1) thrombosis managed initially with thrombolysis and anticoagulation and then referred for surgery, and (2) ...initial treatment with anticoagulation only and later referral for surgery. Definitive benefits of thrombolysis in the acute period (the first 2 weeks after thrombosis) over anticoagulation alone have not been well reported. Our goal was to compare patients managed with early thrombolysis and anticoagulation followed by first rib resection (FRR) and later postoperative venography with venoplasty (PTA) with those managed with anticoagulation alone followed by FRR and PTA using vein patency assessed with venography and standardized outcome measures.
We reviewed a prospectively collected database from 2000 to 2019. Two groups were compared: those managed with early thrombolysis at our institution (Lysis) and those managed with anticoagulation alone (NoLysis). All patients underwent FRR. Venography was routinely performed before and after FRR. Standardized outcome measures included Quick Disability of Arm, Shoulder, and Hand (QuickDASH) scores and Somatic Pain Scale.
A total of 50 Lysis and 50 NoLysis patients were identified. Pre-FRR venography showed that thrombolysis resulted in patency of 98% of veins, whereas 78% of NoLysis veins were patent. After FRR, postoperative venography revealed that 46 (92%) patients in the Lysis group and 37 (74%) patients in the NoLysis group achieved vein patency. Thrombolysis was significantly associated with final vein patency (odds ratio: 17 4-199; P < .001). Lysis patients had a trend toward lower QuickDASH scores from pre-FRR to post-FRR compared with NoLysis patients with a mean difference of −16.4 (±19.7) vs −5.2 (±15.6) points (P = .13). The difference in reduction of Somatic Pain Scale scores was not statistically significant.
Thrombolysis as initial management of PSS, combined with anticoagulation, followed by FFR and VenoPTA resulted in improved final vein patency and may lead to an improved functional outcome measured with QuickDASH scores. Therefore, clinical protocols using thrombolysis as initial management should be considered when planning the optimal treatment strategy for patients with acute PSS.
The liver is an organ that, when dysfunctional in a septic patient, is strongly associated with morbidity and mortality. Understanding the pathophysiology of liver failure during sepsis may lead to ...improved diagnostics and potential therapeutic targets. Historically, programmed cell death receptor (PD) ligand 1 (PD-L1) has been considered the primary ligand for its checkpoint molecule counterpart, PD-1, with PD-L2 rarely in the immunopathological spotlight. PD-1 and PD-L1 contribute to liver dysfunction in a murine cecal ligation and puncture (CLP) model of sepsis, but virtually nothing is known about PD-L2's role in sepsis. Therefore, our central hypothesis was that sepsis-induced changes in hepatic PD-L2 expression contributed to worsened liver function and, subsequently, more pronounced morbidity and mortality. We found that although PD-L1 gene deficiency attenuated the hepatic dysfunction seen in wild-type mice after CLP, the loss of PD-L2 appeared to actually worsen indices of liver function along with a trend toward higher liver tissue vascular permeability. Conversely, some protective effects of PD-L2 gene deletion were noted, such as reduced liver/peritoneal bacterial load and reduced IL-6, IL-10, and macrophage inflammatory protein 2 levels following CLP. These diverse actions, as well as the unique expression pattern of PD-L2, may explain why no overt survival advantage could be witnessed in the septic PD-L2
mice. Taken together, these data suggest that although PD-L2 has some selective effects on the hepatic response seen in the septic mouse, these factors are not sufficient to alter septic mortality in this adult murine model. NEW & NOTEWORTHY Our study shows not only that ligands of the checkpoint protein PD-1 respond inversely to a stressor such as septic challenge (PD-L2 declines, whereas PD-L1 rises) but also that aspects of liver dysfunction increase in septic mice lacking the PD-L2 gene. Furthermore, these differences in PD-L2 gene-deficient animals culminated in the abrogation of the survival advantage seen in the septic PD-L1-knockout mice, suggesting that PD-L2 may have roles beyond a simple immune tolerogen.
We have shown that invariant natural killer T (
NKT) cells mediate sepsis-induced end-organ changes and immune responses, including macrophage bacterial phagocytosis, a finding regulated by the check ...point protein program cell death receptor-1 (PD-1). Furthermore, PD-1 mediates mortality in both adult and neonatal murine sepsis as well as in surgical patients. Given our previous findings, we hypothesize that
NKT cells will also modulate neonatal sepsis survival, and that this effect is regulated in part through PD-1. We utilized a polymicrobial intra-peritoneal cecal slurry (CS) sepsis model in wild type (WT),
NKT
or PD-1
5-7 day old neonatal pups. Typically, tissues were harvested at 24 h for various bioassays/histology and, in some cases, survival was assessed for up to 7 days. Interestingly, similar to what we recently reported for PD-1
mice following CS,
NKT
-deficient animals exhibit a markedly improved survival vs. WT. Histologically, minor alterations in liver architectural, which were noted in WT pups, were attenuated in both
NKT
and PD-1
pups. Following CS, PECAM-1 expression was unchanged in the WT pups but increased in both
NKT
and PD-1
pups. In WT, following CS the emergence of a Ly6C
subpopulation was noted among the influxed peritoneal macrophage population. Conversely, within
NKT
pups, there were fewer peritoneal macrophages and a greater percentage of Ly6C
macrophages. We show not only a key role for
NKT cells in affecting end-organ damage as well as alterations in phagocytes phenotypes in neonatal sepsis but that this
NKT cell mediated effect is driven by the central checkpoint protein PD-1.
Congenital abnormalities of the first rib (ABNFR) are a rare cause of thoracic outlet syndrome (TOS). The range of abnormalities have not been clearly documented in the literature. Surgical ...decompression in these patients presents with increased complexity secondary to anomalous anatomy. Our goal is to review an institutional experience of first rib resection (FRR) performed for ABNFRs, to present a novel classification system, and to analyze outcomes according to clinical presentation.
A prospectively collected database was used to identify individuals with ABNFRs who underwent FRR for TOS between 1990-2021. These individuals were identified both by preoperative imaging and intraoperative descriptions of the first rib after resection. Demographic, clinical, perioperative and pathological data were reviewed. ABNFRs were classified into 3 categories according to anatomical criteria: (I) Hypoplastic, (II) Fused, and (III) Hyperplastic. Outcomes were rated using the standardized Quick Disability of Arm Shoulder and Hand Scores (QDS), Somatic Pain Scores (SPS) and Derkash Scores (DkS).
Among the 2200 cases of TOS, there were 19 patients (0.8%) with ABNFR who underwent FRR. Average age at surgery was 30.5 (range 11–74), including 13 men and 6 women. Presentations included 9 arterial (ATOS), 6 neurogenic (NTOS), and 4 venous (VTOS) cases. There were 6 class I, 6 class II, and 7 class III ABNFRs. Among 6 NTOS patients there were 4 abnormal nerve conduction tests and 5 positive anterior scalene muscle blocks. Among the 9 patients with ATOS, thrombolysis was attempted in 5 patients, and of these, 3 ultimately required surgical thrombectomy. Of 4 VTOS cases, 2 were managed with thrombolysis, and 2 with anticoagulation alone. The approach for FRR was transaxillary in all patients. Secondary procedures included 1 pectoralis minor tenotomy, 1 scalenectomy, and 1 contralateral rib resection. No major neurological or vascular complications occurred. There was 1 patient who required surgical evacuation of a hematoma. Intraoperative chest tube placement was required in 5 patients secondary to pleural entry during dissection. There was an overall improvement in symptoms over an average follow-up of 7.4 months. QDS reduced from 49.7 pre-op to 22.1 (P < 0.05). SPS improved from 3.4 pre-op to 1.8. DkS scores were good to excellent in 79% of patients. Residual symptoms were noted in 7, and ATOS accounted for 5 (70%) of these. All patients were able to return to work.
Despite increased complexity, ABNFRs may be safely resected via transaxillary approach with low incidence of complications, very good symptom relief, and excellent outcomes. Congenital ABNFRs may by classified into 3 categories (hypoplastic, fused, and hyperplastic) with a variety of presentations, including ATOS, NTOS, and VTOS. Classification of ABNFRs allows concise description of abnormal anatomy which facilitates comparison between series and provides direction for surgical management to ultimately optimize patient outcomes.
Patients with acute coronavirus disease 2019 (COVID-19) respiratory infection are associated with concomitant thromboembolic complications and a hypercoagulable state. Although these mechanisms are ...not completely understood, unique alterations in the serum markers for hemostasis and thrombosis have been detected. A high index of suspicion is required by vascular surgeons for patients presenting with this novel virus. We present the case of a 51-year-old man with acute COVID-19 pneumonia who developed phlegmasia cerulea dolens despite chronic warfarin therapy and a supratherapeutic international normalized ratio.
Management of Paget-Schroetter syndrome (PSS) with first rib resection (FRR) and venoplasty is successful in re-establishing subclavian vein (SCV) patency in most cases. However, in cases with ...subacute or chronic venous occlusion, SCV patency may not be achieved. Thus, the role for FRR remains controversial in cases of subacute or chronic SCV occlusion. Our goal is to determine whether FRR is beneficial in PSS patients with subacute or chronic SCV occlusion.
A prospectively maintained thoracic outlet syndrome (TOS) database was searched for patients undergoing FRR who were identified as having SCV occlusion on preoperative venography between 2012 and 2021. Preoperative and postoperative venous patency were determined by venography. Standardized functional outcomes were assessed using the Quick Disability Arm, Shoulder, Hand (QuickDASH—QDS) and Somatic Pain Scale (SPS) before and after FRR. The Derkash outcome score was recorded after FRR.
Over the study period, 966 TOS operations were performed; of these, 401 were for venous TOS, and 33 patients were identified with subacute or chronic preoperative SCV occlusion verified by venography. The median age was 29 years, with 73% men. Eighteen patients had attempted thrombolysis; eight were performed at our institution, and ten performed at a referring facility. The median time from the symptom onset of SCV occlusion to FRR was 78 days for all patients. For the group that achieved venous patency after FRR, the time from SCV occlusion to FRR was 71 days, and it was 106 days for the group that remained occluded after FRR. All underwent postoperative venography and percutaneous attempt at SCV recanalization. Recanalization was successful in 64% (21) and unsuccessful in 36% (12). All patients experienced improvement in SPS and QDS. For all patients, the average SPS improved from 1.69 preoperatively to 0.25 postoperatively and the average QDS improved from 27.63 preoperatively to 10.19 postoperatively (P > .05). For patients who were successfully recanalized, the final SPS was 0.18 and the final QDS was 11.22 (P > .05). In patients who failed to achieve recanalization, the final SPS was 0.40 and the final QDS was 9.06 (P > .05). All postoperative Derkash outcome scores were excellent and good, with none fair or poor.
In patients with subacute or chronic preoperative SCV occlusion, surgical decompression and postoperative angioplasty resulted in re-establishing SCV patency in 64% of patients. Symptomatic patients clinically improve after surgical decompression regardless of whether venous patency is successfully re-established. These results indicate that symptomatic patients with PSS should be considered for TOS decompression even if their SCV is occluded in the subacute or chronic presentation.
Thrombus extension into the deep venous system following superficial vein chemical ablation with Varithena polidocanol microfoam has been reported. The objective of this study was to assess the ...effect of intraoperative improved techniques during treatment for patients with symptomatic varicose veins and their impact on extension of thrombus into deep veins.
A retrospective review of a prospectively maintained database was performed. All patients who underwent endovenous chemical ablation with polidocanol microfoam (Varithena, Boston Scientific, Marlborough, Mass) for symptomatic superficial axial and tributary vein reflux were identified. Patients had postoperative duplex (48-72 hours) scanning after the procedure; those who did not adhere to the recommended follow-up were excluded. Demographic data, CEAP Classification, Venous Clinical Severity Score, procedure details, and follow-up data were abstracted.
Between April 2018 and August 2020, 157 limbs in 122 patients were treated with Varithena microfoam; 129 limbs in 99 patients met our inclusion criteria. Veins treated included the great saphenous vein (n = 89), anterior accessory saphenous vein (n = 15), small saphenous vein (n = 14), and tributary veins (n = 56). Adjunctive techniques during treatment included intraoperative elevation of the limb to greater than 45°, ultrasound mapping and digital occlusion of large perforator veins, limitation of foam volume per session, injection of sterile saline before treatment, and compression of the limb in the elevated position. The preoperative Venous Clinical Severity Score was 11.4 and decreased after treatment to 9.7. The immediate closure rate was 95% with 81% overall symptomatic relief at last follow-up. The mean follow-up was 113.5 days for the entire cohort; two limbs (1.5%) required postoperative anticoagulation for thrombus extension into the deep venous system (common femoral vein n = 1; popliteal vein n = 1) postoperatively for a mean of 22 days. Both resolved with anticoagulation. One asymptomatic limb developed a femoral vein deep venous thrombosis and one symptomatic late deep venous thrombosis was noted 4 months after the procedure. Postoperative pain and phlebitis were reported in 15.6% and 14.8% of patients, respectively, and all had resolved at last follow-up. No pulmonary emboli were noted and no neurologic or visual adverse events were recorded.
Adjunctive techniques during microfoam ablation decreased thrombotic complications in our series compared with those reported in earlier phase III clinical trials. Excellent early closure and symptomatic improvement were also noted. Endovenous microfoam ablation with Varithena is a safe and effective nontumescent, nonthermal alternative to laser and radiofrequency ablation.
Display omitted
PDF
